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Fetal oxygen tension promotes tenascin-C-dependent lung branching morphogenesis.
- Source :
-
Developmental dynamics : an official publication of the American Association of Anatomists [Dev Dyn] 2005 Sep; Vol. 234 (1), pp. 1-10. - Publication Year :
- 2005
-
Abstract
- Tenascin-C (TN-C) is a mesenchyme-derived extracellular matrix (ECM) glycoprotein required for fetal lung branching morphogenesis. Given that the low oxygen (O(2)) environment of the fetus is also essential for normal lung branching morphogenesis, we determined whether fetal O(2) tension supports this process by promoting TN-C expression. Initial studies showed that 15-day fetal rat lung explants cultured for 2 days at 3% O(2) not only branched well, but they also expressed higher levels of TN-C when compared to lungs maintained at 21% O(2), which branched poorly. Antisense oligonucleotide studies demonstrated that TN-C produced in response to 3% O(2) was essential for lung branching morphogenesis. As well, exogenous TN-C protein was shown to promote branching of lung epithelial rudiments cultured at 21% O(2). Because ECM-degrading proteinases are capable of catabolizing TN-C protein, we reasoned that 3% O(2) might promote TN-C deposition by limiting the activity of these enzymes within the fetal lung. Consistent with this idea, gelatin zymography showed that the activity of a 72-kDa gelatinase, identified as matrix metalloproteinase-2 (MMP-2), was lower at 3% O(2) vs. 21% O(2). Furthermore, pharmacologic inhibition of MMP-2 activity in fetal lung explants cultured at 21% O(2) resulted in increased TN-C deposition within the mesenchyme, as well as enhanced branching morphogenesis. Collectively, these studies indicate that fetal O(2) tension promotes TN-C-dependent lung epithelial branching morphogenesis by limiting the proteolytic turnover of this ECM component within the adjacent mesenchyme.<br /> (Copyright 2005 Wiley-Liss, Inc.)
- Subjects :
- Animals
Cell Proliferation
Extracellular Matrix physiology
Gene Expression Regulation, Developmental physiology
Lung physiology
Matrix Metalloproteinase 2 genetics
Matrix Metalloproteinase 2 metabolism
Mesoderm physiology
Rats
Tissue Culture Techniques
Lung embryology
Oxygen physiology
Tenascin physiology
Subjects
Details
- Language :
- English
- ISSN :
- 1058-8388
- Volume :
- 234
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Developmental dynamics : an official publication of the American Association of Anatomists
- Publication Type :
- Academic Journal
- Accession number :
- 16086306
- Full Text :
- https://doi.org/10.1002/dvdy.20500